| Project/Area Number |
09470040
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kanazawa University, Cancer Research Institute |
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Principal Investigator |
SATO Hiroshi Kanazawa University, Cancer Research Institute, Professor, がん研究所, 教授 (00115239)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | MT-MMP / tumor / metastasis / v-src / MDCK / tubular formation / epithelial cells / morphogenesis / 浸潤 / マトリックスメタロプロテアーゼ / ゼラチナーゼA |
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| Research Abstract |
Membrane-type matrix metalloproteinases (MT-MMP) are frequently expressed in human tumor tissues and the level of which is correlated with invasiveness and malignancy of tumors. Thus, MT-MMP is thought to be a key enzyme which trigger tumor metastasis. So far 4 members of MT-MMP have been identified, and among them MT1-MMIP which was discovered for the first time by our group is most closely associated with tumor metastasis. Expression of MT1-MMP is normally observed in mesenchyimal cells e.g. fibroblast and the mechanism of MT1-MMP expression in epithelial cells including carcinoma cells was unclear. In this study we found induction of MT1-MMP expression in canine kidney epithelial cell line MDCK by transformation with oncogenes e.g. v-src and erbB2.
MDCK cells form branching tubules in three-dimensional collagen gel in the presence of Hepatocyte Growth Factor (HGF). This was the first demonstration of morphogen activity of HGF.In this project we demonstrated that MT1-MMP plays an essential role m tubular formation of MDCK cells. MT1-MMP has dual functions, one is to degrade extracellular matrix by itself and the other is to activate precursor form of another matrix metalloproteinase gelatinase A.Using metrix metalloproteinase inhibitors we found that MT1-MMP is involved in kidney tubulogenesis by degrading extracellular matrix by itself rather than through the activation of gelatinase A.In summary we showed that MT1-MMP is induced during not only oncogenic and malignant transformation but also morphogenesis of epithelial cells. In the on-going project we are identifying genes co-expressed with MT1-MMP during oncogenic transformation and morphogenesis by mRNA differential display method, the products of which may contribute to invasive growth of epithelial cells.
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